Pneumolysin PCR-based diagnosis of invasive pneumococcal infection in children

Blood-based pneumolysin PCR was compared to blood culture and detection of pneumolysin immune complexes, as well as to detection of antibodies to pneumolysin and to C polysaccharide, in the diagnosis of pneumococcal infection in 75 febrile children. Invasive pneumococcal infection was suspected on clinical grounds in 67 of the febrile children, and viral infection was suspected on clinical grounds in 8 of the febrile children. In addition, 15 healthy persons were examined to test the specificity of the PCR assay. Plasma, serum, and leukocyte fractions were analyzed by PCR. The combination of all test results led to the diagnosis of pneumococcal infection in 25 patients. Pneumolysin PCR was positive in 44% of these children, an increase occurred in the pneumolysin antibodies in 39% and in the C polysaccharide antibodies in 30% of the patients; pneumolysin immune complexes were found in convalescent serum in 30%, pneumolysin immune complexes occurred in acute-phase serum samples in 16%, and a positive blood culture was found in 20% of the patients. None of the healthy controls had positive results by PCR. The results suggest that the diagnosis of Streptococcus pneumoniae infection from blood samples necessitates the use of several different assays. Pneumolysin PCR was the most sensitive assay, but its clinical value is reduced by the fact that three blood fractions are needed.     

Coeliac disease in Galway, Ireland 1971-1990

Recent studies have reported changes in the incidence of coeliac disease and in its presentation. We carried out a retrospective study looking at the incidence and clinical features of coeliac disease in Galway children over a 20 year period. The study period was divided in two parts. (I) Patients diagnosed between 1971 and 1980 and (II) between 1981 and 1990. Comparison was made between demographic and clinical data in these two periods. There were 97 cases of coeliac disease diagnosed in children resident in Galway over the 20 year period. 71 patients were diagnosed in period I and 26 in period II. The median age at diagnosis in period I was 1.41 years and 4.95 years in period II. There were more females diagnosed in period I. Growth data, histology and enzyme levels were similar in both groups. Diarrhoea and vomiting were the major presenting symptoms in both periods but more patients presented with wasting or abdominal protuberance in the latter period. Our data support the concept that coeliac disease in childhood is declining, and is presenting at a later age.     

Serogroup Y meningococcal disease in Chicago, 1991-1997

CONTEXT: In 1994, surveillance by the Chicago Department of Public Health detected a growing trend in the proportion of invasive meningococcal infections caused by serogroup Y. OBJECTIVE: To examine the emergence of serogroup Y meningococcal disease and compare its clinical characteristics with those of other meningococcal serogroups. DESIGN: Population-based retrospective review of surveillance records; medical record review and cohort analysis of serogroup Y vs non-serogroup Y case patients. SETTING: Chicago, III. PARTICIPANTS: City residents with Neisseria meningitidis isolated from a normally sterile site from January 1, 1991, through December 31, 1997; cohort analysis included those identified through March 31, 1996. MAIN OUTCOME MEASURES: Serogroup-specific incidence, demographics, and clinical outcomes. RESULTS: We identified 214 case patients; 53 (25%) had serogroup Y. The attack rate of serogroup Y meningococcal disease increased from 0.04 cases per 100000 in 1991 to a peak of 0.82 cases per 100000 in 1995 and subsequently decreased to 0.26 cases per 100000 and 0.34 cases per 100000 in 1996 and 1997, respectively. Compared with patients infected by other serogroups, patients with serogroup Y were older (median age, 16 years vs 1 year; P = .001) and more likely to have a chronic underlying illness (prevalence ratio, 2.3; 95% confidence interval, 1.2-4.4). Outcome did not differ significantly between the 2 groups. Multilocus enzyme electrophoresis typing of isolates from 19 case patients identified 5 different types. We found no clustering among the enzyme types by age, race/ethnicity, community area, or time. CONCLUSIONS: Serogroup Y emerged as the most frequent cause of meningococcal disease in Chicago in 1995 and accounted for a substantial proportion of cases in 1996 and 1997. Current data suggest that the magnitude of serogroup Y meningococcal disease is sufficient for vaccine developers to incorporate serogroup Y into new vaccines.     

Infant death rates in Queensland, 1962 to 1972

Published statistical material has been used to analyse the infant death rate in Queensland. The neonatal death rates, which tend to reflect the level of obstetric care, were approximately twice as high in the Peninsula Division as in Brisbane, and the late infant mortality rate was almost eight times as high in the Peninsula Division as in Brisbane. In the Peninsula there has been no fall in infant death rate over the 11 years studied. One small area had an infant mortality rate of 100 deaths per 1,000 live births. The areas with the highest infant death rates were those with a significant Aboriginal population. The data show that proximity to major health facilities does not ensure low infant death rates and in the Brisbane Metropolitan Division there were threefold differences in late infant death rates. It seems likely that infant death rates are influenced by the economic status and education of parents and by the priority they place on infant care. The study has shown that published statistical data can detect areas within Queensland with high infant death rates, and could therfore be used to direct resources to improve the well-being of infants in these areas.     

A more diversified America: state and local population changes, 1990-1997

Recently, the U.S. Bureau of the Census released state and county population estimates with age, gender, race and Hispanic origin detail for 1990-1997. These estimates illustrate the changing demographics of the United States. The 1997 state population estimates show that both Texas and Georgia experienced notable population growth since 1990. Texas replaced New York as the second largest state; Georgia bumped North Carolina from the list of top 10 most populous states to become the state with the 10th largest population. In both Texas and Georgia, migration flows have contributed to the population change. Texas is one of the most popular "intended states of residence" for international migrants, many coming from Latin American countries. On the other hand, Georgia's growth has largely been influenced by "rustbelt" to "sunbelt" domestic migration. At the county level, the largest total population increases again occurred in western and southern states. Population estimates for Asian and Pacific Islanders show that this population remained concentrated in the West in 1997. Similarly, the Hispanic population is primarily concentrated in southwestern states. However, as the Asian and Pacific Islander and Hispanic populations continue to grow, there is spillover into other regions, primarily the larger metropolitan areas in the South, including Washington, DC, and Atlanta, GA. The population projections produced by the Census Bureau indicate that racial and ethnic diversity will continue to increase in the United States well into the next century.     

The clinical impact of resistance in the management of pneumococcal disease

The purpose of this report was to use a particular clinical trial, the Preventive Geriatric Trial (PGT), as a starting point to discuss whether treatment efficacy can be evaluated by means of tooth mortality. In the PGT, 296 subjects were recruited and randomly assigned to five treatment groups: (1) usual procedures (UP); (2) UP + a cognitive-behavioral intervention (CB); (3) UP + CB + weekly chlorhexidine rinse (CHX); (4) UP + CB + CHX + semi-annual fluoride varnish (F); and (5) UP + CB + CHX + F + semi-annual prophylaxis, including scaling (P). Exploratory analyses revealed that tooth mortality after the 1st year was lower in treatment groups 3, 4, and 5 than in groups 1 and 2. A one-year exposure resulted in a 45% reduction in tooth mortality (p < 0.05); a two-year exposure resulted in a 59% reduction (p-value < 0.04). The PGT findings suggested that it is possible to design trials based on clinically relevant endpoints, such as tooth mortality. For the detection of moderate treatment effects, such trials could take the form of Large, Simple Trials (LST), where many subjects are recruited with minimally restrictive entry criteria, and data are collected only on essential baseline characteristics and tooth mortality. LSTs have provided "reliable answers to important clinical questions" for other chronic diseases, and several arguments suggest that they could play a similar critical role in dental research: (1) Periodontitis and caries are among the most common and costly chronic diseases affecting humans, and the identification of even moderately effective treatments by LSTs can have a large socio-economic impact; (2) the identification of low-cost widely practicable treatments that lend themselves to be investigated in LSTs is likely to benefit more people than the identification of high-cost complex treatments; and (3) tooth mortality is simple to assess and more relevant than the unvalidated surrogate endpoints that have largely failed for more than 20 years to provide reliable answers to certain controversial issues regarding treatment efficacy. The cost of not reliably establishing the safety and the efficacy of treatments may be far greater than the cost of conducting LSTs.     

The epidemiology of Haemophilus influenzae invasive disease in Scotland prior to immunisation

Immunisation against Haemophilus influenzae b (Hib) was added to the UK childhood vaccination schedule on 1 October 1992. Based on reports of laboratory isolations from blood and/or CSF, the epidemiology of Haemophilus influenzae invasive disease in Scotland during the last full year before immunisation (1991) is reviewed. In children aged under five years the estimated incidence of infection (25.5 per 100,000) is higher than that previously reported from Scotland, but lower than estimates from Glasgow and other UK studies. However, the age-sex and seasonal distribution is consistent with previous surveys. As in England and Wales, there appears to be regional variation in incidence within Scotland, although this may simply reflect differences in the completeness of laboratory reporting. In addition to 113 laboratory reports of H. influenzae invasive infection, a retrospective search of hospital discharge data and death registrations identified a further 51 and two cases respectively, some of whom may be genuine. In spite of reservations about hospital discharge data, this raises the possibility that there may be an element of under-reporting by laboratories. With the advent of record linkage of hospital discharge data, it would be prudent to monitor the impact of the Hib vaccine programme using this data source in addition to laboratory reports and death registrations.     

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya

BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease. METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture. FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5). In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae. INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.     

Shiga toxin-producing Escherichia coli in finland from 1990 through 1997: prevalence and characteristics of isolates

During the past 10 years Shiga toxin-producing Escherichia coli (STEC) has emerged as one of the most important causes of food-borne infections in industrialized countries. In Finland, with a population of 5.1 million, however, only four STEC O157:H7 infections were identified from 1990 through 1995; the occurrence of non-O157 STEC infections was unknown. In 1996, we established a national prospective study to determine the prevalence of STEC serotypes in feces of Finns with bloody diarrhea. During this enhanced 1-year study period eight sporadic cases of STEC infection were found; of them, only two were indigenously acquired O157:H7 infections. In 1997, O157 infections increased dramatically, with O157 strains causing 51 of all 61 STEC infections. Altogether 14 non-O157:H7 STEC strains were found in Finland in the 1990s: O26:H11 (four strains), O26:HNM (HNM indicates nonmotile), O2:H29, O91:H21, O91:H40, O101:HNM, O107:H27, O157:HNM, O165:H25, OX3:H21, and Rough:H49. All O157:H7 and O26:H11 isolates produced enterohemolysin, but seven of the other STEC strains did not. Most (n = 63) of the 71 STEC strains isolated carried the stx2 gene only, five carried the stx1 gene only, and three carried both genes. The eaeA gene was detected in all other isolates except five non-O157 strains. There were seven distinct pulsed-field gel electrophoresis (PFGE) genotypes among 57 O157 strains and three distinct PFGE types among four O26:H11 strains. The main PFGE type was found among 65% of all O157 isolates.     

Minimally invasive coronary bypass: experience at the Erasme Hospital in 1997-1998

Since the launching of cardiopulmonary bypass in 1952 the landscape of cardiac surgery has been marked by a major milestone every ten years. Though most of the cardiopathies can be surgically treated with satisfactory results in up to 90% of the cases, we must try to improve the existing results. That means--Can we do better, cheaper and less invasive? Several new surgical approaches aiming at so doing are discussed in the present report: Minimally invasive direct coronary arterial bypass (MIDCAB) which is performed through a small anterior thoracotomy; Beating heart revascularization through sternotomy; Heart Port approach; Trans Myocardial Laser Revascularization (TMLR). Those new technologies respectively offer specific advantages to the existing therapies thus represent promising alternatives in selected subcategories of patients.     

Occurrence of IgG subclass antibodies to ovalbumin, avidin, and pneumococcal polysaccharide in children

To validate a previously suggested dosing regimen of aminophylline administration for Thai children, we enrolled 13 asthmatic Thai children (5 girls and 8 boys) between the ages of 7.5-13.4 years (mean = 10.4 years) into a 36-hour, multiple-dose, oral theophylline pharmacokinetic study using plain aminophylline tablets at a dosage of 5 mg of theophylline base/kg every 8 hours. All patients were studied in the steady state. Blood samples were obtained every 2 hours for 24 hours; thereafter, samples were obtained more frequently for another 12 hours to determine theophylline pharmacokinetic parameters. Serum theophylline concentrations (STC) were assayed with a fluorescence polarization immunoassay method (TDX). Significant interpatient variations in STCs were observed. Five patients had peak STCs in the toxic range (> 20 micrograms/ml). Most patients had reproducible STC patterns during the study period; however, marked variations of STCs were observed with a mean percent of fluctuations [(Cmax-Cmin)/Cmin *100] of 535.6%. Using the PC Nonlin computer interpolation program by a modification with a baseline decay method and the Lagrange polynominal interpolation technique, approximate pharmacokinetic parameters were calculated and the results were as follows: plasma half life (t1/2) = 3.08 hours, elimination rate constant (Kel) = 0.26 hour-1, absorption rate constant (Ka) = 2.21 hour-1, volume of distribution (Vd) = 0.23 l/kg and plasma clearance (CI) = 56 ml/kg/hour. Since these calculated parameters could be imprecise due to delayed absorption of oral theophylline dosages, a single-dose intravenous theophylline pharmacokinetic study was further examined in another 18 patients (age range = 7-12 years, mean = 8.9 years) to determine more accurate pharmacokinetic data using intravenous aminophylline at dosage of 5.8 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Authoritarianism in Queensland: a reply to Ray

To examine the hypothesis that the teratogenic effects of the phenothiazine derivative T-82 are due to its causing a riboflavin deficiency day 11 or 12 pregnant CB Wistar rats were each given 2,000 mg/kg T-82 po plus 100 mg/kg riboflavin ip, 12.4 mg/kg ATP ip, or both. The rates of fetal mortality and external malformations were significantly decreased in all supplementation experiments. The frequencies of cleft palate, micrognathia, and micromelia were unchanged but those of ectopic testis and hydrops fetalis were significantly increased in the group treated with T-82 and ATP on day 12.     

Antibiotic resistance in bacterial urinary tract infections, 1991 to 1997

This study assessed changing patterns of antibiotic resistance in Escherichia coli urinary tract infections at a university student health center during three periods: the first 6 months each of 1991, 1994, and 1997. Urine culture and sensitivity results were taken from available medical records of female patients having urine cultures during the three periods (1991, n = 739; 1994, n = 938; 1997, n = 863); age and ethnicity were also noted. In E. coli isolates (the majority of positive cultures), resistance to four antibiotics changed significantly: ampicillin (30% to 45% to 39%), carbenicillin (29% to 42% to 39%), tetracycline (29% to 40% to 23%), and trimethoprim/sulfamethoxazole (15% to 32% to 15%). The results raise questions regarding the future clinical reliability of several commonly used antibiotics in the treatment of urinary tract infection.     

The Leeuwenhoek Lecture, 1997. Marek's disease herpesvirus: oncogenesis and prevention

There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek's disease is the most common and provides excellent opportunities for the study of a herpesvirus-induced tumour both experimentally and under natural conditions in the field. Marek's disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell-associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek's disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek's disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek's disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available. It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional gC, ICP4 for maintaining latency which allows the expression of at least the 1.8 kb family, pp38, meq, and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man-mediated infection with non-pathogenic MDVs.     

Antibody response to pneumococcal polysaccharide vaccine in young, adult and old mice

The anti-pneumococcal antibody response was studied in young (5-week-old) and adult (10-week-old) BALB/c and CBA/J mice and in adult (9-10-week-old) and old (12-, 18- and 24-month-old) AB6F1 and B6D2F1 mice after s.c. immunization with a 23-valent pneumococcal polysaccharide vaccine. Both young and adult mice showed a significant IgM antibody response to the vaccine 6 days after immunization with 1-11 micrograms antigen. There were significant immune responses to serotypes 1, 2, 4 and 7F in contrast to small responses to serotypes 14, 19F and 23F after immunization with the vaccine. One month after immunization, there were only marginal differences in IgM anti-pneumococcal antibody levels to the vaccine (anti-PPS) between immunized and unimmunized BALB/c mice, whereas in CBA/J mice the anti-PPS remained higher in immunized than in unimmunized mice. Immunization of old mice induced a significant IgM antibody response 6 days after immunization, but the anti-PPS thereafter decreased rapidly towards preimmunization values in AB6F1 mice. A significant IgG anti-PPS was not detected in any of the mice studied. The IgA anti-PPS tended to vary over time with no consistent pattern. It is important to carefully consider age and strain of the mice used when studying the immune response to pneumococcal polysaccharide antigens.